PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy?

Abstract

Inhibitory properties of PD-1 receptor engagement on activated T cells are well established in physiologic and pathological contexts. In cancer, the use of checkpoint blockade, such as anti-PD-1 antibodies, becomes progressively a reference treatment of a growing number of tumors. Nonetheless, it is also established that PD-1 expression on antigen-specific T cells reflects the functional avidity and anti-tumor reactivity of these T cells. We will discuss this dual significance of PD-1 expression on tumor-specific T cells, due to a complex regulation and the opportunity to exploit this expression to define, monitor and exploit tumor-reactive T cells for immunotherapy purposes.

Colibactin‐positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer

“…Indeed, anti-PD-1 is supposed to counterbalance T-cell exhaustion and restore the antitumor effector properties of T-cells; thus, the inefficiency of anti-PD-1 in 11G5-infected mice strongly suggests that tumor-specific T-cells are decreased in these mice. 44 In the same way, it was described that induction of IFNγ + /CD8 + T-cell accumulation by gut microbiota manipulation was associated with an increase of anti-PD-1 therapy efficacy in the MC38 graft-model. 45 In addition, the decrease of the CD4 + CD25 + and CD8 + CD25 + T-cells in the MLNs after infection and translocation of the 11G5 E. coli were consistent with the alteration of antitumoral immunity in the colon.…”

“…Even though the antitumor function of T‐cells was not directly investigated in our study, the significant decrease of TILs and the resistance of MC38 tumors to anti‐PD‐1 therapy in 11G5‐infected mice supported the depletion of the tumor‐reactive T‐cell fraction in these mice. Indeed, anti‐PD‐1 is supposed to counterbalance T‐cell exhaustion and restore the antitumor effector properties of T‐cells; thus, the inefficiency of anti‐PD‐1 in 11G5‐infected mice strongly suggests that tumor‐specific T‐cells are decreased in these mice . In the same way, it was described that induction of IFNγ + /CD8 + T‐cell accumulation by gut microbiota manipulation was associated with an increase of anti‐PD‐1 therapy efficacy in the MC38 graft‐model .…”

Presence of few PD‐1‐expressing tumor‐infiltrating immune cells is a potential predictor of improved response to salvage chemotherapy following nivolumab for non‐small cell lung cancer: An exploratory case series

“…In the present study, a low ratio of PD‐1 + cells to immune cells and a small number of PD‐1 + cells were not associated with ORR after nivolumab therapy, but conferred better ORR after salvage chemotherapy. Although the reason for this discrepancy is unclear, recent studies have raised a fundamental question concerning the conflicting roles of PD‐1 on T cells: can PD‐1 expression be considered a reflection of tumor‐specific T cell activation as well as T cell dysfunction in the dynamic process of the tumor immune microenvironment? High PD‐1‐expressing CD8 + cells may be deeply exhausted and irreversibly dysfunctional to PD‐1 blockade followed by salvage chemotherapy.…”

Enhanced Prevention of Breast Tumor Metastasis by Nanoparticle‐Delivered Vitamin E in Combination with Interferon‐Gamma

“…In CD45 + cell cohort, the PD‐1 expression exhibited a slight increase in mice with IFN‐γ and/or NP‐TOS15 treatment (Figure 6C). 40 Therefore, the TME was modulated to facilitate anti‐tumor immunity with the IFN‐γ/NP‐TOS15 combination therapy, almost completely inhibiting lung metastasis compared to the single IFN‐γ or NP‐TOS15 treatment.…”